The past 30-year period of mammalian cloning, viewed by many as the “golden age” of this endeavor, has recently come to a sad close due to the passing of some of its most prominent innovators. It was on September 10, 2023, that Sir Ian Wilmut (OBE, FRS, FMedSci, FRSE) of Dolly fame passed away aged 79. [1] Very soon thereafter, on September 27, 2023, the scientific community was dealt another blow with the passing of 95-year-old Ryuzo Yanagimachi DSc, yet another leading pioneer in in the domain of biotechnology and cloning. [2] More recently, on May 21, 2024, the medical community mourned the loss of cloning pioneer Mark Westhusin, Ph.D, at the age of 66. [3] It is the objective of this Perspective to review the accomplishments of the aforementioned luminaries as well as to highlight the profound significance thereof.

Sir Ian Wilmut, a native of Hampton Lucy, Warwickshire, England, served as the Chair of the Scottish Centre for Regenerative Medicine at the Roslin Institute of the University of Edinburgh. It was in 1996 that Sir Wilmut, a developmental biologist and the leader of a research team of investigators, broke new ground by achieving the cloning of a mammal from an adult somatic cell taken from a mammary gland. [4] As is well known globally, “the world’s most famous sheep” was the product of the electrofusion of sheep mammary-derived cells with enucleated sheep oocytes. [4] The newborn, a Finnish Dorset lamb named Dolly, was thus the outcome of somatic nuclear transfer in kee** with the pioneering efforts of John B. Gurdon, PhD, whose efforts entailed the use of sexually mature members of Xenopus laevis origin. [5]

Professor Ryuzo Yanagimachi, a Japanese-born American-based scientist, yet another prominent leader in the field of cloning, served for close to 60 years as faculty in the Department of Anatomy and Reproductive Biology at the John A. Burns School of Medicine of the University of Hawaii at Manoa. In his groundbreaking paper of 1998, Professor Yanagimachi describes the injection of enucleated mouse oocytes by his postdocs—inspired and encouraged by the great professor—with cumulus cell nuclei, which ultimately resulted in the full-term development of mice, of which Cumulina was the first. [6] On the other hand, Yanagimachi underlines the fact that “Sertoli or neuronal nuclei developed in vitro and implanted following transfer…none developed beyond 8.5 days post coitum; however, a high percentage of enucleated oocytes receiving cumulus nuclei developed in vitro.” [6] In summarizing his seminal findings, Professor Yanagimachi concluded that “for mammals, nuclei from terminally differentiated, adult somatic cells of known phenotype introduced into enucleated oocytes are capable of supporting full development.” [6].

Similar efforts to achieve nuclear transfer have been made under the direction of Mark Westhusin, Professor of Veterinary Physiology and Pharmacology (VTPP) at the School of Veterinary Medicine and Biomedical Sciences (VMBS) of Texas A&M University in College Station, Texas, USA. It was in fact Professor Westhusin who created the first genetic clones of a house cat (COPYCAT or CC) in 2001. [7] Parallel efforts have given rise to the generating of white-tailed deer, cows, and goats. Other VBMS teams have, from their side, undertaken the cloning of pigs and horses.

Viewed from today’s perspective, the notion of somatic nuclear transfer in any and all mammalian species is hardly a novelty. Rather, it is, in ethically responsible and capable hands, an important and versatile tool. Most recently, this very technology enabled further advances in the burgeoning field of in vitro gametogenesis (IVG). [8] Although many are undoubtedly deserving of gratitude for bringing us this far, special thanks are certainly due to Sir Ian Wilmut, Professor Ryuzo Yanagimachi, and Professor Ryuzo Yanagimachi!